ERCC6L drives lung adenocarcinoma metastasis: a PJA2/p53 ubiquitination-dependent mechanism.

IF 5.8 2区医学 Q1 Medicine

Respiratory Research Pub Date : 2026-04-30 DOI:10.1186/s12931-026-03692-5

Lingyu Jiang, Huaihai Zhou, Shengjing Liang, Zhaoke Wen, Junqi Qin, Zhenniu Lei, Rongling Li, Yunzhi Ma, Shucong Peng, Yifan Zhou, Yonglong Zhong

{"title":"ERCC6L drives lung adenocarcinoma metastasis: a PJA2/p53 ubiquitination-dependent mechanism.","authors":"Lingyu Jiang, Huaihai Zhou, Shengjing Liang, Zhaoke Wen, Junqi Qin, Zhenniu Lei, Rongling Li, Yunzhi Ma, Shucong Peng, Yifan Zhou, Yonglong Zhong","doi":"10.1186/s12931-026-03692-5","DOIUrl":null,"url":null,"abstract":"<p><p>Lung adenocarcinoma (LUAD) is prone to metastasis and exhibits a poor prognosis. The DNA repair-related protein ERCC6L is implicated in tumorigenesis, but its role in LUAD invasion and metastasis remains unclear. The expression, function, and underlying mechanisms of ERCC6L were investigated using bioinformatics analysis, cellular assays, and animal experiments. ERCC6L was significantly upregulated in LUAD tissues and cell lines, and its high expression was associated with poor overall and recurrence-free survival. Functional experiments demonstrated that ERCC6L overexpression promoted the migration, invasion, and epithelial-mesenchymal transition (EMT) of LUAD cells. Mechanistically, ERCC6L activated the E3 ubiquitin ligase PJA2, which mediated K48-linked polyubiquitination and subsequent degradation of p53, thereby attenuating its tumor-suppressive function. In vivo studies confirmed that ERCC6L knockout suppressed tumor growth, metastasis, and EMT progression by regulating the PJA2/p53 signaling axis. ERCC6L promotes migration, invasion, and EMT in LUAD by facilitating PJA2-mediated ubiquitination and degradation of p53. The ERCC6L/PJA2/p53 axis represents a potential novel therapeutic target for inhibiting metastasis in LUAD.</p>","PeriodicalId":49131,"journal":{"name":"Respiratory Research","volume":" ","pages":""},"PeriodicalIF":5.8000,"publicationDate":"2026-04-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Respiratory Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s12931-026-03692-5","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}

引用次数: 0

Abstract

Lung adenocarcinoma (LUAD) is prone to metastasis and exhibits a poor prognosis. The DNA repair-related protein ERCC6L is implicated in tumorigenesis, but its role in LUAD invasion and metastasis remains unclear. The expression, function, and underlying mechanisms of ERCC6L were investigated using bioinformatics analysis, cellular assays, and animal experiments. ERCC6L was significantly upregulated in LUAD tissues and cell lines, and its high expression was associated with poor overall and recurrence-free survival. Functional experiments demonstrated that ERCC6L overexpression promoted the migration, invasion, and epithelial-mesenchymal transition (EMT) of LUAD cells. Mechanistically, ERCC6L activated the E3 ubiquitin ligase PJA2, which mediated K48-linked polyubiquitination and subsequent degradation of p53, thereby attenuating its tumor-suppressive function. In vivo studies confirmed that ERCC6L knockout suppressed tumor growth, metastasis, and EMT progression by regulating the PJA2/p53 signaling axis. ERCC6L promotes migration, invasion, and EMT in LUAD by facilitating PJA2-mediated ubiquitination and degradation of p53. The ERCC6L/PJA2/p53 axis represents a potential novel therapeutic target for inhibiting metastasis in LUAD.

查看原文本刊更多论文

ERCC6L驱动肺腺癌转移：PJA2/p53泛素化依赖机制

肺腺癌（LUAD）易发生转移，预后较差。DNA修复相关蛋白ERCC6L与肿瘤发生有关，但其在LUAD侵袭和转移中的作用尚不清楚。通过生物信息学分析、细胞分析和动物实验研究了ERCC6L的表达、功能和潜在机制。ERCC6L在LUAD组织和细胞系中显著上调，其高表达与较差的总生存率和无复发生存率相关。功能实验表明，ERCC6L过表达可促进LUAD细胞的迁移、侵袭和上皮间质转化（EMT）。在机制上，ERCC6L激活E3泛素连接酶PJA2，介导k48相关的多泛素化和随后的p53降解，从而减弱其肿瘤抑制功能。体内研究证实，ERCC6L敲除通过调节PJA2/p53信号轴抑制肿瘤生长、转移和EMT进展。ERCC6L通过促进pja2介导的泛素化和p53降解，促进LUAD的迁移、侵袭和EMT。ERCC6L/PJA2/p53轴代表了抑制LUAD转移的潜在新治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Respiratory Research RESPIRATORY SYSTEM-

CiteScore

9.70

自引率

1.70%

发文量

314

审稿时长

4-8 weeks

期刊介绍： Respiratory Research publishes high-quality clinical and basic research, review and commentary articles on all aspects of respiratory medicine and related diseases. As the leading fully open access journal in the field, Respiratory Research provides an essential resource for pulmonologists, allergists, immunologists and other physicians, researchers, healthcare workers and medical students with worldwide dissemination of articles resulting in high visibility and generating international discussion. Topics of specific interest include asthma, chronic obstructive pulmonary disease, cystic fibrosis, genetics, infectious diseases, interstitial lung diseases, lung development, lung tumors, occupational and environmental factors, pulmonary circulation, pulmonary pharmacology and therapeutics, respiratory immunology, respiratory physiology, and sleep-related respiratory problems.